Abstract
BackgroundThe role of neutrophil gelatinase-associated lipocalin (NGAL) as a diagnostic marker for acute kidney injury (AKI) in sepsis is still debated. We hypothesized that in sepsis, the performance of serum(s) and urinary(u) NGAL can be negatively impacted by severity of illness and inflammation, and that both uNGAL and sNGAL levels can be increased regardless of presence of AKI.MethodsOne hundred and seven patients with sepsis were included. uNGAL and sNGAL were measured at admission (T0) and 4 hours (T4) and 24 hours later (T24). Transient and intrinsic AKI were respectively defined as AKI according to RIFLE during the first 72 hours that did or did not recover to “no AKI” in the following 72 hours. Patients were classified according to tertiles of CRP and APACHE II score increase. The relationship between sNGAL and uNGAL was assessed by linear regression.ResultsFifty-seven patients developed transient and 22 intrinsic AKI. Prevalence of transient and intrinsic AKI were higher in patients with versus without septic shock (OR (95% CI):3.3(1.4-8.2)). uNGAL was associated with sNGAL, and this with parallel slopes but different intercepts for AKI (Y = 0.87*X + 314.3,R2 = 0.31) and no AKI (Y = 0.87*X + 20.1,R2 = 0.38). At T4, median uNGAL and sNGAL levels were higher in septic patients with versus without shock but this is independent of AKI ((545 ng/mL vs 196 ng/ml for uNGAL and 474 ng/ml vs 287 ng/ml for sNGAL (both P = 0.003)). Both uNGAL and sNGAL levels increased with tertiles of CRP and APACHE II score increase.ConclusionsSerum and uNGAL levels are influenced by severity of illness and inflammation, and this was found to be independent of the presence of AKI. There is a strong correlation between sNGAL and uNGAL levels in patients with sepsis, indicating that increased levels of uNGAL can also be due to overspill from the systemic circulation, blurring the discriminative value of NGAL as a biomarker for AKI in patients with sepsis.
Highlights
The role of neutrophil gelatinase-associated lipocalin (NGAL) as a diagnostic marker for acute kidney injury (AKI) in sepsis is still debated
We found a strong correlation between sNGAL and uNGAL, both in patients without and with AKI (R2 = 0.38 for no AKI and R2 = 0.31 for AKI), but with different relationships in no AKI (Y = 0.87*X + 20.1) versus AKI (Y = 0.87*X + 314.3), respectively (P < 0.001)
There was a significant difference in uNGAL levels between no AKI, transient AKI and intrinsic AKI, this difference did not remain when patients were stratified according to severity of sepsis and to tertiles of C-reactive protein (CRP) or APACHE II score increase, except for sNGAL in the highest CRP tertile where a significant difference between AKI and no AKI could be found
Summary
The role of neutrophil gelatinase-associated lipocalin (NGAL) as a diagnostic marker for acute kidney injury (AKI) in sepsis is still debated. Septic acute kidney injury (AKI) is associated with worse outcome compared to non-septic AKI and is regarded as a distinct clinical entity [1]. Diagnosis of septic or non-septic AKI remains cumbersome because it relies on imperfect parameters such as serum creatinine while introduction of new serum and urinary biomarkers could hypothetically allow earlier diagnosis and better prognostication [7,8,9]. NGAL (neutrophil gelatinase-associated lipocalin) has been the most frequently investigated biomarker for early diagnosis of AKI [10]. Three different forms of NGAL can be found, namely a 25 kDa monomer, a 45 kDa dimer and a 135 kDa heterodimer, covalently conjugated with gelatinase [11,12,13]. No commercially available immunoassays are able to make a clear discrimination between the monomer, mainly released from tubular epithelial cells, and the dimer, originating from neutrophils [12]
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